Research funding from the The Paul G. Allen Family Foundation will support four projects focused on extracellular vesicles

Uncovering biological properties of extracellular vesicles, which play a vital role in how cells communicate, and understanding how sex hormones drive behavior and development are two areas that the new cohorts of Allen Distinguished Investigators will research, thanks to over $10 million in funding from the Paul G. Allen Family Foundation. The 18 researchers will develop technologies, design approaches, and uncover insights into fundamental areas of human biology.

The Paul G. Allen Family Foundation will award $1.5 million to seven research projects which 18 researchers will lead. Together, these awards represent a total of approximately $10.5 million in funding from the Foundation, as recommended by The Paul G. Allen Frontiers Group, to support cutting-edge, early-stage research projects that promise to advance the fields of biology and medicine. The seven awarded projects were selected from open calls for proposals in two fields: extracellular vesicles and sex hormones. When considering funding areas, The Frontiers Group looks for emerging fields where an investment could be catalytic to advance scientific progress—not just for awardees, but for all in that particular field.

“Our two newest cohorts of Allen Distinguished Investigators are using innovative technologies and unprecedented ambition to pioneer new frontiers in the fields of sex hormones and extracellular vesicles. These discoveries have the potential to not only change and challenge our current understanding of basic biological principles but also are poised to reveal significant implications in human health.” said Kathy Richmond, Ph.D., M.B.A., Executive Vice President and Director of the Frontiers Group and the Office of Science and Innovation at the Allen Institute.

Meet the New Allen Distinguished Investigators Researching Extracellular Vesicles

Extracellular vesicles hold huge promise as a means of therapeutic delivery; however, their diversity and a lack of understanding of their basic biology are hindering progress. This cohort seeks to elucidate fundamental principles of the biology of extracellular vesicles in a variety of contexts, including the development of technologies to better visualize and track them in living organisms.

Composition and functionality of the EV corona: learning from lipoproteins

  • Kenneth Witwer, Ph.D., Johns Hopkins University School of Medicine
  • Angela M. Zivkovic, Ph.D., University of California, Davis
  • Wyatt N. Vreeland, Ph.D., National Institute of Standards and Technology

In this project, researchers will investigate a recently recognized feature of extracellular vesicles (EVs) known as the “EV corona,” a layer of molecules that may imbue EVs with specialized properties. Researchers will use advanced analytical methods to detect and identify the molecules of the EV corona and map them with unprecedented detail. Additionally, they will bioengineer EVs by linking their surfaces directly to specific proteins of the corona to disguise the EVs from the body’s immune system. Doing so is important because EVs can be used to diagnose and treat diseases; however, exogenous EVs may be attacked by the immune system before their therapeutic benefits can be exerted. Allowing them to remain in the body longer could lead to better therapies and treatments for disease.

Blood-brain Barrier communication via extracellular vesicles underlying brain function and behavior

  • Shinichi Kano, M.D., Ph.D., University of Alabama at Birmingham

A significant challenge with treatments for brain disorders is the lack of efficient drug delivery systems into the brain. As part of this research project, Shinichi Kano and his team will examine the mechanisms by which extracellular vesicles (EVs) can cross the blood-brain barrier to gain entry into the brain and identify the core molecules of EVs and their recipient cells that allow them to influence neurons. The proposed study will reveal new insights into the foundational mechanisms by which EVs act within the body. The study will also generate extensive datasets that could contribute to developing novel EV-inspired drug delivery systems for the brain.

Extracellular vesicles in maintenance of neuronal circuitry

  • Andrew Chisholm, Ph.D., University of California San Diego
  • Ann Wehman, Ph.D., University of Denver

In this project, researchers will examine the role extracellular vesicles (EVs) play in helping neurons maintain their shape. Failure to maintain neuronal shape can lead to impaired brain function or neurodegeneration. Changes in the function of proteins that regulate EV release can restore healthy neuron shape in animals, suggesting regulation of EVs maintains neuronal shape. Moreover, researchers have found that such EV regulators affect the shape of other cell types such as skin or germ cells. This project will take a multidisciplinary approach including microscopy, protein design, and genetics to learn how these factors affect cellular shape in worms and mammals and develop novel probes for EV-related lipids. The results may reveal how EVs contribute to neuronal resilience, with implications for brain health.

Real-time label-free dynamic imaging of extracellular vesicles in live tissues

  • Marni D. Boppart, Sc.D., University of Illinois at Urbana-Champaign
  • Stephen A. Boppart, M.D., Ph.D., University of Illinois at Urbana-Champaign

Researchers Marni and Stephen Boppart will use next-generation, multimodal, nonlinear optical microscopy techniques to obtain real-time, dynamic images of EVs in living tissues and use this advanced platform to identify the role EVs play in human aging. Recent studies suggest that aged cells secrete EVs carrying materials that promote aging throughout the body. However, no tools currently exist to effectively study EVs in the natural tissue microenvironment. This project will not only yield a powerful microscopy platform that will provide the first visualization of EV dynamics within a complex living tissue microenvironment but will also provide new insight regarding fundamental EV biology in the context of multiple conditions, including aging and disease.

SourceThe Allen Institute

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